Computational Design of an Intramolecular Photocyclization Reaction with State-Selective Reactivity: A Strategy for Indole Synthesis

Development of efficient and convenient indole synthesis method is of great methodological and pharmaceutical interest. In this work, by developing and applying a de novo visible-light-induction-based design strategy to exploit the electron transition and [1, 6]-H shift, we have discovered an intramolecular photocyclization of carbonyl and tertiary amine for indole synthesis without relying on the photocatalyst. Our elaborate quantum mechanics (QM) calculations revealed the ‘state-selective reactivity’ feature of this reaction, and the different substrate types can achieve different yields through this feature. Furthermore, our extensive synthetic experiments confirmed that the different substrate types could produce significantly different yields. This new insight into the interplay between the ‘state-selective reactivity’ and the yields emphasizes its importance and gives guidance regarding ‘state-selective reactivity’ for the high yield of various indole derivatives.